Kerr told NBC Sports Bay Area the Dubs must "prepare" to play the entire campaign without the sharpshooter, even though they've previously left the door open for a late-season return.
"It's unlikely that he's going to play this year," Kerr said. "So we have to understand that."
He added: "You have to look at it realistically. I had an ACL [tear] in college, and I missed a whole season. Generally, an ACL for a basketball player is a full-year recovery, and if it's a full year for Klay, that puts them out for the season."
Kerr later clarified his remarks:
Thompson suffered the injury during the 2019 NBA Finals, which saw the Warriors fall to Kawhi Leonard and the Toronto Raptors in six games.
Kerr's comments came after the guard's father, former NBA forward Mychal Thompson, provided a far more optimistic timetable during an interview on 95.7 The Game (via Drew Shiller of NBC Sports Bay Area).
"I'm hoping sometime in March," the elder Thompson said Wednesday. "There's no definitive date, but that would be nine months from the injury. As long as he's dedicated and determined in his rehab. He's got a great physical therapy staff. He'll know before March—sometime in February or January—how he's feeling going through all the basketball drills."
The Warriors will lean more heavily on younger guards, led by Jacob Evans and Jordan Poole, to fill the void behind starters Stephen Curry and D'Angelo Russell.
"We have to prepare our young guys to fill that role behind him, and when he gets back, whenever that is, hopefully these young guys now are developed and in the rotation and ready to really be contributors on a playoff team and we can get better," Kerr told NBC Sports Bay Area.
Between Thompson's injury and the departure of Kevin Durant, whose status for the upcoming season with the Brooklyn Nets is also up in the air because of an Achilles injury suffered during the Finals, leaves Golden State with an unsettled outlook after years of being the league's predominant favorite.
Caesars Sportsbook still lists the Warriors tied with the Houston Rockets for the third-best odds to win the Western Conference at +450. They trail only the Los Angeles Lakers (+185) and Los Angeles Clippers (+225).
The Dubs open the regular season Thursday night against the Clippers at 10:30 p.m. ET on TNT.